Staphylococcus aureus is a leading human bacterial pathogen that is a common source of infections in healthcare and community environments. The 2013 Center for Disease Control (CDC) report on antibiotic resistance prioritized methicillin-resistant Staphylococcus aureus (MRSA) as an ongoing serious threat, with 2011 records indicating that 11,285 of the 23,000 deaths caused by antibiotic-resistant bacteria and fungi in the US were directly attributed to MRSA infections. Due to the difficulty in calculating exact mortality rates, these figures are given as conservative estimates and the actual numbers are thought to be higher. The financial cost incurred by hospitals and clinics is even more difficult to measure, but a study from 2009 estimated that a MRSA infection that takes place during surgery could cost a hospital $60,000 per patient in additional procedures and extended hospital stay.
Overall, the number of serious MRSA infection cases in healthcare situations has diminished. However, over the past decade there has been a steady rise in the number of community-associated (CA) infections. If this trend continues and new strains of MRSA show further resistance to existing antibiotics, the CDC intends to upgrade the threat level from serious to urgent. In addition the financial burden imposed by CA-MRSA infection has been estimated at $7,070-$20,489 per patient, at an annual cost of $1.4-$3.8 billion to society. For these reasons the discovery of new classes of antibiotics for treatment of MRSA infections, especially orally available antibiotics, is essential.
Antibiotics that are approved for treatment of MRSA infections are vancomycin (a glycopeptide), linezolid (an oxazolidinone), daptomycin (a lipopeptide) and more recently, ceftaroline (a β-lactam) and tedizolid (an oxazolidinone). Only linezolid and tedizolid are orally bioavailable among these agents. Furthermore, resistance to each of these antibiotics is known. Accordingly, there is a need for new classes of antibiotics, and particularly new classes of antibiotics that are effective against resistant strains of bacteria, including bacteria that are resistant to beta-lactam antibiotics.